cas9 Enhances Bacterial Virulence by Repressing the regR Transcriptional Regulator in Streptococcus agalactiae
cas9 Enhances Bacterial Virulence by Repressing the regR Transcriptional Regulator in Streptococcus agalactiae
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DOI：
10.1128/iai.00552-17
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发表时间：
2018-03-01
影响因子：
3.1
通讯作者：
Liu, Yongjie
中科院分区：
文献类型：
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作者：
Ma, Ke;Cao, Qing;Liu, Yongjie
CRISPR及其相关的cas基因已被证明在许多病原体中调节自身基因和毒力。在这项研究中，我们发现cas9的失活导致鱼无乳链球菌菌株GD 201008 -001的粘附和细胞内存活减少，并显著降低了该菌株在斑马鱼和小鼠中的毒力。进一步的研究表明，regR转录调节因子在Delta cas9突变体中上调。由于regR介导透明质酸酶的抑制，透明质酸酶是参与打开小鼠血脑屏障（BBB）的关键因子，cas9介导的regR转录的抑制对于S.无乳症打开血脑屏障，从而导致动物脑膜炎。这项研究扩展了我们对细菌中CRISPR-Cas系统介导的内源性基因调控的理解。
Clustered regularly interspaced palindromic repeats (CRISPR) and their associated cas genes have been demonstrated to regulate self-genes and virulence in many pathogens. In this study, we found that inactivation of cas9 caused reduced adhesion and intracellular survival of the piscine Streptococcus agalactiae strain GD201008-001 and significantly decreased the virulence of this strain in zebrafish and mice. Further investigation indicated that the regR transcriptional regulator was upregulated in the Delta cas9 mutant. As regR mediates the repression of hyaluronidase, a critical factor involved in opening the blood-brain barrier (BBB) in mice, cas9-mediated repression of regR transcription is important for S. agalactiae to open the BBB and thereby cause meningitis in animals. This study expands our understanding of endogenous gene regulation mediated by CRISPR-Cas systems in bacteria.